The promise of using growth factors to improve bone healing has not yet been realized. Gene therapy with viral vectors coding for growth factor genes may have clinical utility because it prolongs exposure to the cytokine of interest. We will evaluate the activity of SF/HGF, a pleiotropic growth factor, as a protein and in a gene activated matrix in an animal model of femoral gap defect. In Specific Aim I we will examine the effects of rhSF/HGF on angiogenesis and healing. In Specific Aim 2 we will study the effects of treating with SF/HGF gene activated matrix in the same animal model. The results from these studies will provide the basis for a Phase II project to develop gene therapy with SF/HGF for clinical applications. PROPOSED COMMERCIAL APPLICATIONS: The project proposed will generate new information on the role of an important cytokine, scatter factor hepatocyte growth factor (SF/HGF) for promoting regeneration of bone. Inadequate healing is a significant cause of morbidity and compromised quality of life in patients with osteoporotic and non-healing bone fractures. The collective costs of treating these patients is more than $9 billion per annum in flee U.S. If the studies are successful, Angion Biomedica will pursue a Phase II program to provide the basis for clinical development of SF/HGF gene therapy for bone regeneration.